A nucleotide code governs Lis1's ability to relieve dynein autoinhibition.

Dynein-1 is a microtubule motor responsible for the transport of cytoplasmic cargoes. Activation of motility requires it first overcome an autoinhibited state prior to its assembly with dynactin and a cargo adaptor. Studies suggest that Lis1 may relieve dynein's autoinhibited state.

Optimizing post-surgical outcomes: unveiling the importance of patient-reported outcomes with insights from the schulthess local shoulder arthroplasty registry.

Objective: The establishment of clinical registries is essential for the comprehensive evaluation of surgical outcomes. In 2006, the Schulthess Shoulder Arthroplasty Registry (SAR) was launched to systematically assess safety, implant longevity, functional outcomes, pain levels, quality of life, and patient satisfaction in individuals undergoing shoulder arthroplasty. This paper aims to outline the registry data and demonstrate how it is leveraged to improve clinical outcomes.

Inhibition of p38-MK2 pathway enhances the efficacy of microtubule inhibitors in breast cancer cells.

Microtubule-targeting agents (MTAs) have been successfully translated from basic research into clinical therapies and have been widely used as first- and second-line chemotherapy drugs for various cancers. However, current MTAs exhibit positive responses only in subsets of patients and are often accompanied by side effects due to their impact on normal cells. This underscores an urgent need to develop novel therapeutic strategies that enhance MTA efficacy while minimizing toxicity to normal tissues.

The role of kinetochore dynein in checkpoint silencing is restricted to disassembly of the corona.

During mitosis, kinetochore-microtubule attachments are monitored by a molecular surveillance system known as the spindle assembly checkpoint. The prevailing model posits that dynein evicts checkpoint proteins (e.g.

Pulse Oximetry and Race in Critically Ill Adults.

Unlabelled: For critically ill adults, oxygen saturation is continuously monitored using pulse oximetry (Spo) as a surrogate for arterial oxygen saturation (Sao). Skin pigmentation may affect accuracy of Spo by introducing error from statistical bias, variance, or both. We evaluated relationships between race, Spo, Sao, and hypoxemia (Sao < 88%) or hyperoxemia (Pao > 150 mm Hg) among adults receiving mechanical ventilation in a medical ICU.

Predictive blood biomarkers of sheep pregnancy and litter size.

Early detection of sheep pregnancy and the prediction of how many lambs a pregnant ewe delivers affects sheep farmers in a number of ways, most notably with regard to feed management, lambing rate, and sheep/lamb health. The standard practice for direct detection of sheep pregnancy and litter size (PLS) is ultrasonography. However, this approach has a number of limitations.

Evaluation of Long-Term Outcomes of Femoropopliteal Bypass Surgery in Patients With Chronic Limb-Threatening Ischemia in an Endovascular Era.

Background: To investigate the long-term outcomes of femoropopliteal bypass surgery in patients with chronic limb-threatening ischemia (CLTI) and TransAtlantic Inter-Society Consensus II (TASC II), type D (TASC D) femoropopliteal disease.

Methods: A retrospective analysis was performed for all consecutive patients undergoing above-knee (AK) femoropopliteal bypass surgery at an academic vascular centre between January 2007 and March 2019. Patients with claudication (IC) and patients with CLTI were included.

Prescription Opioid Characteristics and Nonfatal Overdose Among Patients Discharged from Tennessee Emergency Departments.

Background: Despite increasing trends of nonfatal opioid overdoses in emergency departments (EDs), population-based studies comparing prescription opioid dosing patterns before and after nonfatal opioid overdoses are limited.

Objectives: To evaluate characteristics of prescribing behaviors before and after nonfatal overdoses, with a focus on opioid dosage.

Methods: Included were 5,395 adult residents of Tennessee discharged from hospital EDs after a first nonfatal opioid overdose (2016-2017).

Evaluation of circulating cell-free KRAS mutational status as a molecular monitoring tool in patients with pancreatic cancer.

Background: Pancreatic carcinoma carries a devastating prognosis and is the 4th leading cause for cancer related death in the US and most European countries. Apart from imaging and CA 19-9, pancreatic carcinoma is still lacking reliable markers to assess tumor dynamics and to monitor treatment response over time. The aim of this study was to evaluate the feasibility of cell free tumor-DNA (cft-DNA), respectively KRAS mutation in peripheral blood, detection as a prognostic and predictive value for chemotherapy monitoring.

Modeling a disease-correlated tubulin mutation in budding yeast reveals insight into MAP-mediated dynein function.

Mutations in the genes that encode α- and β-tubulin underlie many neurological diseases, most notably malformations in cortical development. In addition to revealing the molecular basis for disease etiology, studying such mutations can provide insight into microtubule function and the role of the large family of microtubule effectors. In this study, we use budding yeast to model one such mutation-Gly436Arg in α-tubulin, which is causative of malformations in cortical development-in order to understand how it impacts microtubule function in a simple eukaryotic system.

Correction: Diagnostic value of partial exome sequencing in developmental disorders.

[This corrects the article DOI: 10.1371/journal.pone.

Candidate serum metabolite biomarkers of residual feed intake and carcass merit in sheep.

Mutton and lamb sales continue to grow globally at a rate of 5% per year. However, sheep farming struggles with low profit margins due to high feed costs and modest carcass yields. Selecting those sheep expected to convert feed efficiently and have high carcass merit, as early as possible in their life cycle, could significantly improve the profitability of sheep farming.

New insights into the mechanism of dynein motor regulation by lissencephaly-1.

Lissencephaly ('smooth brain') is a severe brain disease associated with numerous symptoms, including cognitive impairment, and shortened lifespan. The main causative gene of this disease - lissencephaly-1 (LIS1) - has been a focus of intense scrutiny since its first identification almost 30 years ago. LIS1 is a critical regulator of the microtubule motor cytoplasmic dynein, which transports numerous cargoes throughout the cell, and is a key effector of nuclear and neuronal transport during brain development.

Pac1/LIS1 stabilizes an uninhibited conformation of dynein to coordinate its localization and activity.

Dynein is a microtubule motor that transports many different cargos in various cell types and contexts. How dynein is regulated to perform these activities with spatial and temporal precision remains unclear. Human dynein is regulated by autoinhibition, whereby intermolecular contacts limit motor activity.

Synthesis of Poly-Sodium-Acrylate (PSA)-Coated Magnetic Nanoparticles for Use in Forward Osmosis Draw Solutions.

The synthesis of magnetic nanoparticles (MNPs) coated with hydrophilic poly-sodium-acrylate (PSA) ligands was studied to assess PSA-MNP complexes as draw solution (DS) solutes in forward osmosis (FO). For MNP-based DS, the surface modification and the size of the MNPs are two crucial factors to achieve a high osmolality. Superparamagnetic nanoparticles (NP) with functional groups attached may represent the ideal DS where chemical modifications of the NPs can be used in optimizing the DS osmolality and the magnetic properties allows for efficient recovery (DS re-concentration) using an external magnetic field.

Molecular basis for dyneinopathies reveals insight into dynein regulation and dysfunction.

Cytoplasmic dynein plays critical roles within the developing and mature nervous systems, including effecting nuclear migration, and retrograde transport of various cargos. Unsurprisingly, mutations in dynein are causative of various developmental neuropathies and motor neuron diseases. These 'dyneinopathies' define a broad spectrum of diseases with no known correlation between mutation identity and disease state.

Effectors of the spindle assembly checkpoint are confined within the nucleus of Saccharomyces cerevisiae.

The spindle assembly checkpoint (SAC) prevents erroneous chromosome segregation by delaying mitotic progression when chromosomes are incorrectly attached to the mitotic spindle. This delay is mediated by mitotic checkpoint complexes (MCCs), which assemble at unattached kinetochores and repress the activity of the anaphase promoting complex/cyclosome (APC/C). The cellular localizations of MCCs are likely critical for proper SAC function, yet remain poorly defined.